alternatives to cytology: new perspectives for screening of cervical cancer - s. nazeer · 2016. 6....

Hôpitaux Universitaires de Genève


Alternatives to Cytology: New Perspectives for Screening of Cervical Cancer

Saloney NAZEER


Objective of the Project

• To evaluate the feasibility, applicability and cost-effectiveness of different approaches to screening of cervical cancer in different resource settings


Annual Estimates of New Cases Globally

Incidence Mortality

• Breast Cancer 795 000 313 000

• Cervical Cancer 450 000 300 000

• Ovarian Cancer 165 000 101 000

• Endometrial Cancer 142 000 42 000

WHO/IARC, 1999


Incidence of Cervix uteri cancer ASR (World) All ages


Available Control Strategies

Strategy Cases (%) Deaths (%)Tobacco 20 30Diet 25 20Infections 15 10Screening 3 4

Cervix 60 60Breast 0 25

Treatment 0 20


Time to show Important Impact of Different Measures

Prevention Time (in yrs)Tobacco 30Diet 10-50Infections 40Screening 5-10Treatment 5


Prerequisites of a successful screening programme

A CANCER is suitable for screening if:• a cancer is a major health problem justifying

screening• natural history of disease - long enough detectable

pre clinical phase • significant proportion of preclinical lesions

progress to clinical disease• available acceptable treatment


Screening Test

• is valid for identifying preclinical lesions• acceptable (to patient & physician)• screening interval• affordable


Characteristics of an Organized Screening Program

• Identification of target Population • Measures for high coverage and attendance• Clear screening protocol: health objectives• Adequate field facilities• Adequate facilities for diagnosis, Rx and FU • Information system (cancer registry)• Evaluation and monitoring (Process and Outcome

quality indicators)


Pap Smears

• Sensitivity: 11 to 99% • Specificity: 14 to 97%• False negative: 5 to 55%

-Errors of Commission: laboratory errors-1/3-Errors of Ommission: sampling errors-2/3

• CostsFahey et al , 1995


Alternatives to Cytology• Visual Inspection of the cervix

Simple - Clinical DownstagingAcetic Acid Aided - VIA

• Gynoscopy• Cervicography• Speculoscopy• Fournier transformed Infrared Spectroscopy• Laser induced Fluorescence• HPV Detection / vaccines


( INCGC )

WHO International Study Group

INTERNATIONAL NETWORK ON CONTROL OF GYNAECOLOGICAL

CANCERS

Hôpitaux Universitaires de GenèveWHO COLLABORATING CENTRE FOR RESEARCH IN HUMAN REPRODUCTION


INCGCThe Philosophy/Aims&Objectives

• To establish collaboration amongst International Players

• To standardise research methdology• To translate research findings into interventions

“Model Protocol for RCT / Demonstration Project”


Pilot Demonstration Project for cervical cancer Screening &

Management in a Selected Region in Pakistan

(Lahore District)

In collaboration with WHO & MOH Pakistan


Estimated Cases of Cx Ca in Regions andSelected Countries

Region/Country• North America• Latin America• Europe• USSR• Africa• China• India• Japan• Other Asian • Australia/NZ

source:WHO,1999

New Cases/Year • 15 700• 44 000• 47 200• 31 300• 36 900• 131 500• 120 000• 9 700• 70 300• 1 200


Cervical Cancer in Pakistan: Epidemiology

• Total population - 130 million• Rural population - 70%• Male/Female ratio - 45:55• Community - Muslims (90%); Christians;

Zorostrians• Literacy rate - 30%


Cervical Cancer in Pakistan: Epidemiology

Hospital based data:• 3rd common cancer in women

(following Breast & Oral CA)• 60% of all genital tract CA• 70-80% stage III / IV• 89% in the age group 30-55 yrs• Majority in low socio-economic class


Objectives of the Project

• evaluate effect of health education• evaluate VIA as a screening test• evaluate performance of cytology• evaluate feasibility, acceptability & cost-benefit

of different screening methods


AIM of the Project

• To devise a national screening programme in Pakistan for Cervical Cancer


Materials & MethodsProject Areas:• Lahore District - population of 700 000• Three rural and periurban areas - CHUNG,

RAIWIND and BURKI • Comparable socio-economic & demographic

backgrounds• Similar health care facilities• Equal access to the district's teaching hospitals ,

namely Sir Ganga Ram Hospital and Mayo Hospital


Project Phases:

• PHASE I PREPARATORYJune 1996 - September 1996

• PHASE II INTERVENTIONJanuary 1997- June 1997

- Knowledge Attitude and Practice (KAP) Survey- Health Education- Training

• PHASE III - Data CollectionJuly 1997 - December 1998


Target Population

• Total female Population: ± 50 000• Target Population (WHO criteria )• Sexually active women aged 30-60 years: ±

15 000• Population census data


Data Collection

• KAP SurveyPreprepared questionnaire by lady health workers

• Screening & ManagementAll women aged 30-60 yrs, who presented at thehospital gynae.out-patient clinics(June 1997 - Dec. 1998)


Methodology1080 women - aged 30-60 yrs

M/H - Gynae examination

VIA - 3% A.A.

Acetowhite lesion No Acetowhite lesion

Papsmear conventional

Colposcopy - SGRH Recall 3 yrs

Punch Bx/histology

CIN I: Rx infec. Rpt 12 wksCIN II: Cryo or elec. CoagCIN III: Cold knife cone


RESULTSKAP Survey• No. of women (30-60 yrs): 15 000• Education: 85% uneducated / 15% primary school• Mean age at marriage: 20.6 yrs• Parity: 0-15 ( >25% had >5 children) • Low socio-economic status• Knowledge about general health: poor• Knowledge about cervical cancer: 0%• Reluctance to visit a clinic if not ill: 100%


RESULTS

Screening & Management

• No.of women: 1080• Age: 30-60 yrs ( median 40.2 )• All were married with median parity of 7.5


Results of VIA and Pap-smears comparedwith Histologic diagnosis

VIA PAP No. Lost Colposcopy Biopsy Mild Disp. Mod. Disp. Severe Disp CIS Inv. Ca Other100 10 90 66 4 6 24 16 12 4212 32 180 90 6 56 8 2 0 1856 16 40 10 6 2 2 0 0 0712 20 204 12 4 4 0 0 0 4

1080 78 514 178 20 68 34 18 12 26TOTAL


Results ( contd.)

• Histology was the reference point

• Dysplasia all grades: 14 %LSIL - 2%HSIL - 12%

• Invasive cancer: 1.2%


Comparison of VIA and Histology

VIA Total134 22 15618 4 22

Total 152 26 178

Histology


Comparison of Pap-smear and Histology

Pap Smear Total72 4 7680 22 102

Total 152 26 178

Histology


RESULTS

sensitivity specificity false neg

• Pap-smear 47.4% 84.6% 53.6%

• VIA 88.1% 15.4%


Consensus Consensus Conference, Tunis 1999 Conference, Tunis 1999 AIMS & OBJECTIVESAIMS & OBJECTIVES

• Review & assess completed & ongoing research studies on Cx Ca /HPV/STD and their relevance to screening for Cx Ca

• Review & revise, current WHO Guidelines• Revise strategies to successfully carry out these

recommendations esp. in DCs


VIASTUDY TYPE of

STUDYSCREENING TESTS PATIENT

POPULATIONRESULTS

University of Zimbabweand JHPIEGOZimbabwe 1999

Cross-sectional

• VIA Age 25-55yrs attendingPHC clinics.

Sensitivity: 76.7%Specificity: 64.1%

• PapColposcopy/Biopsy

44.3%90.6%

T.Wright et alCape Town 1999

Cross-sectional

• Pap• VIA• HPV• Cerviograpy

35-60 yrsPeri-urban communityunscreened

78/95%67/84%58/92%73/86%

Singh et alDelhi1999

ongoing……

???

• VIA• Gyno• Cyto• (colpo/histo)

3000 women HSIL

81.5%88.9%88.9%80%

Croije et alBloemfontein1997-1999

ongoing…..

??• Cyto• Cervico• VIA

• Cyto• Cervico• VIA• Speculo

3000 women

1000 women

37.8%/9950.3% /77%51.2%/ 49%

60/96%48.9/86.8%80/46.3%82/ 39.5%


Human Papilloma Virus ( HPV)

STUDY TYPE ofSTUDY

SCREENING TEST PATIENTPOPULATION

RESULTS

Lorincz et alNew York 1998

Cohort Study Hybrid Capture Liquid Based Cytology

Biopsy

265 women withASCUS and LSIL

by Colposcopy( mean age 27yrs)

Sensitivity:LSIL 86%HSIL 93%

Kinney et alUSA 1999

Cohort Study Liquid based cytologyHybrid Capture

Histology

995 women withASCUS fromGynae Clinics

SensitivityHPV – 89.2%

Repeat Pap 76.2%Cuzick et al

UK 1999Cross -

sectionalConventional Pap

PCR /SHARPHybrid Capture

3103 women, > 35yrs

Routine GP Clinics

PCR= 87.3%HPV Hybrid Capture

=88.9%Pap –79%

T.Wright et alCape Town

Cross-sectional

CytologyVIA

Hybrid CaptureCervicography

1415 women36-60 yrs

67.9% sensitivity ofboth HPV Hybrid

Capture ( selfcollected) and Pap


Different Screening Methods Compared to PapSmearTEST LINKS SCIENTIFIC T SE/SP C TEPap + + + ? ?

PolarProbe + ? ? ? ? +

VIA + + +- ? -Automa

tion - + ++ + +

Speculoscopy + + ? ? + -

TumorMarker - + ? ? ? + +

Cervicography - + +- + -

ThinPrep - + + + ? +

HPVTest - + -- ? +

HPVVaccine + + +

DownStaging + --

T = Training - SE = Sensitivity - C = Cost - TE = TechnologyLinks = Means referrals when compared to Pap test


Conclusion / Discussion



• Screening for cervical cancer reduces incidence of & mortality from invasive disease (upto 90%)

• Is applicable as a public health policy

• However, a single format cannot be applicable for all countries / regions



• Limitations of cytology based screening programmes (esp in DCs):- cost for population based application- lack of quality assurance - suboptimal- logistical issues

• Low compliance / High drop out rate


Conclusion / DiscussionNew alternative techniques - holding promise

• VIA sensitivity comparable (70%)specificity low (14-30%)

? PPV & NPV? Efficacy & QC? Cost ( overtreatment)


Conclusion / Discussion• HPV sensitivity comparable (80-90%)

specificity lower (high false + < 30 yrs)

? PPV & NPV (risk of reduced surveillance)? Efficacy & QC? Cost ( pop. based screening)? Benefit independent of cytology


Conclusion / Discussion• Sequential screening with a low cost, simple test

e.g. Visual Inspection with Acetic Acid (VIA)

• Followed by a more objective test e.g. Pap smear or HPV detection on selected sub-group

• Disinvest in screening programme (screen 10 yrly)



• All new techniques need to be evaluatedin RCTs for specificity; quality control; cost-effectiveness; efficacy

• HPV vaccines: 30 years to evaluate; logistics not defined



Pap smear the only proven method Step-up approach• Screen every woman at age 45• When resources permit screen 10 yrly at age 35,

45, 55• If resources available, screen 5 yrly age 35-59• Once coverage achieved (80%)- expand to age 25

(if resources available)


Cervical Cancer Control27

Mortality in developing countries

Screening introducedin developed countries

Effect of screening

6

Mortality in developed countries

Effect ofhealth education visual inspectionstandard therapy

Dea

ths

0,0

per 1

000

time


Parting Comment

The decision to establish and continue screeningprogrammes depends on:

• the factual evidence

• a compromise between different elements of progmmmes, individualised to the needs of different populations

Alternatives to Cytology: New Perspectives for Screening of Cervical CancerObjective of the ProjectAnnual Estimates of New Cases GloballyAvailable Control StrategiesTime to show Important Impact of Different MeasuresPrerequisites of a successful screening programmeScreening TestCharacteristics of an Organized Screening ProgramAlternatives to CytologyWHO International Study Group INTERNATIONAL NETWORK ON CONTROL OF GYNAECOLOGICAL CANCERSINCGC The Philosophy/Aims&ObjectivesPilot Demonstration Project for cervical cancer Screening & Management in a Selected Region in Pakistan (Lahore District)Estimated Cases of Cx Ca in Regions and Selected CountriesCervical Cancer in Pakistan: EpidemiologyCervical Cancer in Pakistan: EpidemiologyObjectives of the ProjectAIM of the ProjectMaterials & MethodsProject Phases:Target PopulationData CollectionRESULTSRESULTSResults of VIA and Pap-smears compared with Histologic diagnosisResults ( contd.)Comparison of VIA and HistologyComparison of Pap-smear and HistologyRESULTSConsensus Conference, Tunis 1999 AIMS & OBJECTIVESVIADifferent Screening Methods Compared to PapSmearConclusion / DiscussionConclusion / DiscussionConclusion / DiscussionConclusion / DiscussionConclusion / DiscussionConclusion / DiscussionConclusion / DiscussionParting Comment

alternatives to cytology: new perspectives for screening of cervical cancer - s. nazeer · 2016. 6....

Documents